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Promising new developments in cancer chemotherapy.
K Ferrante1, B Winograd, R Canetta
1Bristol-Myers Squibb Pharmaceutical Research Institute, Richard L. Gelb Center for Pharmaceutical Research and Development, Wallingford, CT 06492-7660, USA. ferrantk@bms.com
Cancer Chemotherapy and Pharmacology
|June 5, 1999
Summary
New cancer therapies are emerging, including microtubule-targeting agents like paclitaxel, oral platinum compounds such as satraplatin, and novel inhibitors of enzymes like topoisomerase and matrix metalloproteinases (MMPs). These advancements offer improved treatment options for various solid tumors and drug-resistant cancers.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Traditional chemotherapeutics have shown survival benefits, driving interest in newer cytotoxic and orally active agents with better therapeutic indices.
- Advances in understanding human tumorigenesis pathways have led to mechanism-based targeted therapies.
- Microtubules, targeted by taxanes like paclitaxel, are crucial for inhibiting mitotic progression and inducing apoptosis.
Purpose of the Study:
- To review novel anticancer agents and therapeutic strategies under investigation.
- To highlight compounds targeting microtubules, platinum-based therapies, and enzyme inhibitors.
- To discuss emerging approaches including vaccination strategies and targeting oncogenes/tumor suppressor genes.
Main Methods:
- Review of preclinical and clinical data for novel anticancer agents.
- Focus on compounds with improved efficacy, oral bioavailability, and targeted mechanisms.
- Exploration of therapeutic strategies including vaccination and gene-targeted therapies.
Main Results:
- Paclitaxel and its analogues demonstrate efficacy in various solid tumors by stabilizing microtubules.
- Oral platinum compounds (e.g., satraplatin) and chemopotentiators (e.g., DPPE) show promise, including in cisplatin-resistant lines.
- Dual topoisomerase inhibitors (TAS-103), MMP inhibitors, and farnesyltransferase inhibitors targeting Ras pathways exhibit significant preclinical antitumor activity.
Conclusions:
- Novel therapeutic approaches targeting microtubules, platinum compounds, specific enzymes, and oncogenic pathways offer significant potential for future cancer chemotherapy.
- Vaccination strategies and MMP inhibitors are being investigated for specific cancer settings and tumor progression.
- Ongoing research by Bristol-Myers Squibb Pharmaceutical Research Institute is yielding promising candidates for effective cancer treatment.